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Resveratrol Attenuates Meningitic Escherichia coli-Mediated Blood-Brain Barrier Disruption
Ruicheng Yang1, Yujin Lv1,2, Ling Miao1
1State Key Laboratory of Agricultural Microbiology, The Cooperative Innovation Center for Sustainable Pig Production, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
Abstract:
Meningitic Escherichia coli can infiltrate the central nervous system (CNS), consequently increasing the levels of proinflammatory cytokines and chemokines and deteriorating the integrity of the blood-brain barrier (BBB). Resveratrol has emerged in recent years as a compound with antioxidant and anti-inflammatory properties. However, it is still unknown how resveratrol affects meningitic E. coli-induced CNS dysfunction. Here, by using in vivo and in vitro BBB models, we demonstrated that resveratrol treatment significantly inhibited meningitic E. coli invasion of the BBB, protected the integrity of the BBB, and reduced neuroinflammation and lethality. In mechanism, resveratrol inhibited bacterial penetration of the BBB by attenuating the upregulation of caveolin-1 (CAV-1), a class of lipid rafts maintaining endothelial cell function. Resveratrol treatment also maintained BBB permeability by suppressing the ERK1/2-VEGFA signaling cascade. In vivo treatment of resveratrol decreased the production of inflammatory cytokines and improved the survival rate in mice challenged with meningitic E. coli. These findings collectively indicated that resveratrol could attenuate meningitic E. coli-induced CNS injury, which might constitute a new approach for future prevention and treatment of E. coli meningitis.
Insights
Resveratrol protects the central nervous system (CNS) from E. coli meningitis by inhibiting bacterial invasion and reducing neuroinflammation. This compound shields the blood-brain barrier (BBB), offering a potential new treatment for E. coli-induced CNS injury.
Area of Science:
- Neuroscience
- Infectious Diseases
- Pharmacology
Background:
- Meningitic *Escherichia coli* (E. coli) can breach the central nervous system (CNS), leading to increased inflammation and blood-brain barrier (BBB) damage.
- Resveratrol, a known antioxidant and anti-inflammatory agent, has potential therapeutic applications, but its effect on *E. coli*-induced CNS dysfunction is not well understood.
Purpose of the Study:
- To investigate the protective effects of resveratrol against meningitic *E. coli*-induced CNS injury.
- To elucidate the underlying mechanisms by which resveratrol mitigates *E. coli* invasion and neuroinflammation.
Main Methods:
- Utilized *in vivo* and *in vitro* models of the blood-brain barrier (BBB).
- Assessed the impact of resveratrol on *E. coli* invasion, BBB integrity, neuroinflammation markers, and survival rates in mice.
- Investigated the molecular mechanisms involving caveolin-1 (CAV-1) and the ERK1/2-VEGFA signaling pathway.
Main Results:
- Resveratrol significantly inhibited *E. coli* invasion of the BBB and protected its integrity.
- Treatment with resveratrol reduced neuroinflammation, decreased inflammatory cytokine production, and improved survival rates in mice.
- Mechanistically, resveratrol attenuated caveolin-1 (CAV-1) upregulation and suppressed the ERK1/2-VEGFA signaling cascade, maintaining BBB permeability.
Conclusions:
- Resveratrol demonstrates significant protective effects against *E. coli*-induced CNS injury.
- Resveratrol attenuates neuroinflammation and preserves BBB integrity by modulating specific molecular pathways.
- These findings suggest resveratrol as a potential therapeutic strategy for preventing and treating *E. coli* meningitis.
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